Stroke Literature Synopses: Basic Science
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Damage-associated molecular pattern mediators (DAMPs), also known as alarmins, are evolutionarily conserved biomolecules that can initiate and perpetuate a sterile/noninfectious inflammatory response after tissue injury. Three recent studies reported how DAMPS/alarmins are involved in stroke pathology.
Shichita et al (MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1. Nat Med. 2017;23:723–732. doi: 10.1038/nm.4312)
examined the mechanisms of clearance of DAMPs after stroke. High-mobility-group box 1 (HMGB1), peroxiredoxins, and S100A8/A9 proteins are well-characterized DAMPs that are involved in brain injury. The authors isolated cells from day 3 postischemic mouse brain (male C57BL/6; 8–14 weeks; 60 minutes middle cerebral artery occlusion by filament insertion) and incubate the cells with fluorescence-labeled recombinant peroxiredoxins, HMGB1, and S100A8/A9. Immunostaining and fluorescence-activated cell sorter experiments confirmed that those DAMPs were selectively internalized by infiltrating mononuclear phagocytes. Then, using a macrophage-like cell line RAW264.7, the authors established mutant clones that were deficient in the …